Plaquette expectation value and gluon condensate in three dimensions

In three dimensions, the gluon condensate of pure SU(3) gauge theory has ultraviolet divergences up to 4-loop level only. By subtracting the corresponding terms from lattice measurements of the plaquette expectation value and extrapolating to the continuum limit, we extract the finite part of the gluon condensate in lattice regularization. Through a change of regularization scheme to MSbar and (inverse) dimensional reduction, this result would determine the first non-perturbative coefficient in the weak-coupling expansion of hot QCD pressure.Comment: 11 page

Fidelity of primary care nurses' delivery of a behavioural change intervention enhancing physical activity in patients at risk of cardiovascular disease: an observational study

Objective To evaluate the fidelity of delivery of a nurse-led intervention to enhance physical activity in patients at risk for cardiovascular diseases, the Activate intervention, by assessing: (1) self-reported fidelity of delivery; (2) observed fidelity of delivery; (3) quality of delivery of the Activate intervention and (4) nurses' beliefs about their capability, motivation, confidence and effectiveness towards delivering the Activate intervention, including behavioural change techniques.Design An observational study.Setting General practices in the Netherlands.Participants Primary care nurses (n=20) from 16 general practices.Primary and secondary outcome measures Nurses' self-reported fidelity was evaluated using checklists (n=282), and the observed fidelity and quality of delivery were examined using audiorecordings of consultations of the delivery of the Activate intervention (n=42). Nurses' beliefs towards delivering the intervention were assessed using questionnaires (n=72).Results The self-reported fidelity was 88.1% and observed fidelity was 85.4%, representing high fidelity. The observed fidelity of applied behavioural change techniques was moderate (75.0%). The observed quality of delivery was sufficient and varied among nurses (mean 2.9; SD 4.4; range 0-4). Nurses' beliefs about their capability, motivation, confidence and effectiveness towards delivering the intervention increased over time.Conclusions Nurses delivered most intervention components as intended with sufficient quality. Nurses believed they were capable, motivated and confident to deliver the intervention. They believed the intervention was effective to increase patients' physical activity level. Despite the high fidelity and moderate fidelity of applied behavioural change techniques, the varying quality of delivery within and across nurses might have diluted the effectiveness of the Activate intervention.Cardiolog

SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages

Immune cells are armed with Toll-like receptors (TLRs) for sensing and responding to pathogens and other danger cues. The role of extracellular-signal-regulated kinases 1/2 (Erk1/2) in TLR signaling remains enigmatic, with both pro- and anti-inflammatory functions described. We reveal here that the immune-specific transmembrane adaptor SCIMP is a direct scaffold for Erk1/2 in TLR pathways, with high-resolution, live-cell imaging revealing that SCIMP guides the spatial and temporal recruitment of Erk2 to membrane ruffles and macropinosomes for pro-inflammatory TLR4 signaling. SCIMP-deficient mice display defects in Erk1/2 recruitment to TLR4, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. Our findings thus delineate a selective role for SCIMP as a key scaffold for the membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages

New insights into chasmosaurine (Dinosauria: Ceratopsidae) skulls from the Upper Cretaceous (Campanian) of Alberta, and an update on the distribution of accessory frill fenestrae in Chasmosaurinae

Chasmosaurine ceratopsids are well documented from the Upper Cretaceous (Campanian) Dinosaur Park Formation (DPF) of southern Alberta and Saskatchewan, and include Chasmosaurus belli, Chasmosaurus russelli, Mercuriceratops gemini, Vagaceratops irvinensis, and material possibly referable to Spiclypeus shipporum. In this study, we describe three recently prepared chasmosaurine skulls (CMN 8802, CMN 34829, and TMP 2011.053.0046) from the DPF, and age-equivalent sediments, of Alberta. CMN 8802 and CMN 34829 are both referred to Chasmosaurus sp. based on the size and shape of the preserved parietal fenestrae. TMP 2011.053.0046 is referred to Vagaceratops sp. based on the position and orientation of its preserved epiparietals. Each skull is characterized by the presence of an accessory fenestra in either the squamosal (CMN 8802 and TMP 2011.053.0046) or parietal (CMN 34829). Such fenestrae are common occurrences in chasmosaurine squamosals, but are rare in the parietal portion of the frill. The origin of the fenestrae in these three specimens is unknown, but they do not appear to exhibit evidence of pathology, as has been previously interpreted for the accessory fenestrae in most other chasmosaurine frills. These three skulls contribute to a better understanding of the morphological variation, a

First records of a plesiosaurian (Reptilia: Sauropterygia) and an ichthyosaur (Reptilia: Ichthyosauria) from Yukon, Canada

An isolated centrum collected ex situ from marine shales of the Lower Cretaceous (Albian) Arctic Red Formation along the Road River represents the first documented occurrence of a plesiosaurian from Yukon. This centrum represents the northernmost occurrence of plesiosaurians in the Western Interior Sea of North America prior to the establishment of the first continuous seaway (Western Interior Seaway) connecting the Boreal and Tethyan seas. Additionally, this centrum is potentially the secondoldest elasmosaurid specimen known from North America. A second centrum, collected along the Beaver River, is likely derived from the Lower Cretaceous (Lower Albian) Garbutt Formation exposed farther upstream. It represents the first report of an ichthyosaur from Yukon. Additionally, six associated ribs collected from the Arctic Re

Mass spectra of doubly heavy Omega_QQ' baryons

We evaluate the masses of baryons composed of two heavy quarks and a strange quark with account for spin-dependent splittings in the framework of potential model with the KKO potential motivated by QCD with a three-loop beta-function for the effective charge consistent with both the perturbative limit at short distances and linear confinement term at long distances between the quarks. The factorization of dynamics is supposed and explored in the nonrelativistic Schroedinger equation for the motion in the system of two heavy quarks constituting the doubly heavy diquark and the strange quark interaction with the diquark. The limits of approach, its justification and uncertainties are discussed. Excited quasistable states are classified by the quantum numbers of heavy diquark composed by the heavy quarks of the same flavor.Comment: 14 pages, revtex4-file, 3 eps-figures, 5 tables, typos correcte

A New Liver Expression Quantitative Trait Locus Map From 1,183 Individuals Provides Evidence for Novel Expression Quantitative Trait Loci of Drug Response, Metabolic, and Sex-Biased Phenotypes

Expression quantitative trait locus (eQTL) studies in human liver are crucial for elucidating how genetic variation influences variability in disease risk and therapeutic outcomes and may help guide strategies to obtain maximal efficacy and safety of clinical interventions. Associations between expression microarray and genome-wide genotype data from four human liver eQTL studies (n = 1,183) were analyzed. More than 2.3 million cis-eQTLs for 15,668 genes were identified. When eQTLs were filtered against a list of 1,496 drug response genes, 187,829 cis-eQTLs for 1,191 genes were identified. Additionally, 1,683 sex-biased cis-eQTLs were identified, as well as 49 and 73 cis-eQTLs that colocalized with genome-wide association study signals for blood metabolite or lipid levels, respectively. Translational relevance of these results is evidenced by linking DPYD eQTLs to differences in safety of chemotherapy, linking the sex-biased regulation of PCSK9 expression to anti-lipid therapy, and identifying the G-protein coupled receptor GPR180 as a novel drug target for hypertriglyceridemia

Lipopolysaccharide promotes Drp1-dependent mitochondrial fission and associated inflammatory responses in macrophages

Mitochondria have a multitude of functions, including energy generation and cell signaling. Recent evidence suggests that mitochondrial dynamics (i.e. the balance between mitochondrial fission and fusion) also regulate immune functions. Here, we reveal that lipopolysaccharide (LPS) stimulation increases mitochondrial numbers in mouse bone marrow‐derived macrophages (BMMs) and human monocyte‐derived macrophages. In BMMs, this response requires Toll‐like receptor 4 (Tlr4) and the TLR adaptor protein myeloid differentiation primary response 88 (MyD88) but is independent of mitochondrial biogenesis. Consistent with this phenomenon being a consequence of mitochondrial fission, the dynamin‐related protein 1 (Drp1) GTPase that promotes mitochondrial fission is enriched on mitochondria in LPS‐activated macrophages and is required for the LPS‐mediated increase in mitochondrial numbers in both BMMs and mouse embryonic fibroblasts. Pharmacological agents that skew toward mitochondrial fusion also abrogated this response. LPS triggered acute Drp1 phosphorylation at serine 635 (S635), followed by sustained Drp1 dephosphorylation at serine 656 (S656), in BMMs. LPS‐induced S656 dephosphorylation was abrogated in MyD88‐deficient BMMs, suggesting that this post‐translational modification is particularly important for Tlr4‐inducible fission. Pharmacological or genetic targeting of Tlr4‐inducible fission had selective effects on inflammatory mediator production, with LPS‐inducible mitochondrial fission promoting the expression and/or secretion of a subset of inflammatory mediators in BMMs and mouse embryonic fibroblasts. Thus, triggering of Tlr4 results in MyD88‐dependent activation of Drp1, leading to inducible mitochondrial fission and subsequent inflammatory responses in macrophages.Ronan Kapetanovic, Syeda Farhana Afroz, Divya Ramnath, Grace MEP Lawrence, Takashi Okada, James EB Curson, Jost de Bruin, David P Fairlie, Kate Schroder, Justin C St John, Antje Blumenthal, Matthew J Swee

Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.

BACKGROUND: Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa. METHODS: We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR). RESULTS: We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2). CONCLUSIONS: PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection

Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion.

IL-1β requires processing by caspase-1 to generate the active, pro-inflammatory cytokine. Acute IL-1β secretion from inflammasome-activated macrophages requires caspase-1-dependent GSDMD cleavage, which also induces pyroptosis. Mechanisms of IL-1β secretion by pyroptotic and non-pyroptotic cells, and the precise functions of caspase-1 and GSDMD therein, are unresolved. Here, we show that, while efficient early secretion of endogenous IL-1β from primary non-pyroptotic myeloid cells in vitro requires GSDMD, later IL-1β release in vitro and in vivo proceeds independently of GSDMD. IL-1β maturation is sufficient for slow, caspase-1/GSDMD-independent secretion of ectopic IL-1β from resting, non-pyroptotic macrophages, but the speed of IL-1β release is boosted by inflammasome activation, via caspase-1 and GSDMD. IL-1β cleavage induces IL-1β enrichment at PIP2-enriched plasma membrane ruffles, and this is a prerequisite for IL-1β secretion and is mediated by a polybasic motif within the cytokine. We thus reveal a mechanism in which maturation-induced IL-1β trafficking facilitates its unconventional secretion